Brief Communication

Acute Effects of Exercise on Cognition in Patients with Chronic Obstructive Pulmonary Disease
CHARLES F. EMERY, VANESSA J. HONN, DAVID J. FRID, KIM R. LEBOWITZ, and PHILIP T. DIAZ
Department of Psychology and Department of Medicine, Ohio State University, Columbus, Ohio Prior data indicate positive effects of long-term exercise interventions for cognitive functioning among patients with chronic obstructive pulmonary disease (COPD), but no prior studies have examined acute effects of individual bouts of exercise among patients with COPD. This study evaluated acute effects of exercise on cognitive performance in a community-based sample of patients with COPD and a healthy control group, matched by age, sex, and education. Twenty-nine older adults with COPD (mean age 67.8 yr [ 7.4]; range: 5685; 17 women) and 29 matched healthy control subjects (mean age 68.7 yr [ 6.0]) were recruited from the community. All participants completed a 20-min exercise session in which they exercised to a peak level and a video control condition in which they were provided information about exercise and cholesterol. Conditions were separated by a 1-wk interval, and order of participation in conditions was randomly assigned. Assessments of cognitive performance (Trail Making Test, Digit Symbol, Verbal Fluency, Digit Span, Finger Tapping) were administered before and after each condition (exercise and video). Among patients with COPD, acute exercise was associated with improved performance on the Verbal Fluency test, a measure of verbal processing, suggesting that acute exercise may benefit aspects of cognitive performance among patients with COPD. Keywords: aerobic exercise; cognition; COPD

Past studies of patients with chronic obstructive pulmonary disease (COPD) indicate that participation in a regular exercise program is associated with improvements in physical functioning (1), reduction in dyspnea (2), and positive changes in mood (3). In addition, data have indicated improved cognitive/ neuropsychologic performance among patients with COPD following a 10-wk aerobic exercise program (4). Cognitive performance is of particular relevance in this population because prior research has documented cognitive deficits among hypoxemic patients with COPD (5), and cognitive deficits may contribute to impaired quality of life (e.g., confusion, problem-solving difficulty, memory problems). Exercise is thought to contribute to improved cognitive performance as a result of cumulative physical and psychologic changes occurring over the course of multiple exercise training sessions. Evidence supporting this mechanism of improvement has been provided in studies of healthy older adults that have documented improved cognitive performance following exercise programs of 1012 wk (6, 7).

(Received in original form April 30, 2001; accepted in final form August 9, 2001) This study was supported by a grant from the National Heart, Lung, and Blood Institute. Correspondence and requests for reprints should be addressed to Charles F. Emery, Department of Psychology, Ohio State University, 1885 Neil Avenue, Columbus, OH 43210. E-mail: emery.33@osu.edu Am J Respir Crit Care Med Vol 164. pp 16241627, 2001 DOI: 10.1164/rccm2104137 Internet address: www.atsjournals.org

Prior studies have not determined the amount of exercise necessary to produce cognitive benefits. Indeed, it has been suggested that individual bouts of exercise may have a positive effect on cognitive performance. Although past studies have not evaluated acute exercise effects among patients with COPD, two prior studies of older adult samples provide encouraging data. In a study of 15 older adults (10 men; 5 women) with complaints of memory loss or cognitive impairment, significant improvement was observed on measures of memory and general cognitive ability following 45 min of light aerobic exercise (8). A second study of 20 older adult (mean age 84.5 yr) nursing home residents (3 men, 17 women) found that semantically cued memory was significantly improved in an exercise group, but not among subjects in a video-watching condition (9). Although these two studies provide support for an acute effect of exercise on cognitive performance, the studies had several methodologic weaknesses including nonrepresentative samples (i.e., older adults with memory complaints, residents of a nursing home), absence of documentation of exercise performance, and variability in the social component of the exercise experience (i.e., group exercise versus individual exercise). Furthermore, neither of the studies evaluated patients with COPD. As patients with COPD are increasingly encouraged to participate in exercise rehabilitation as the standard of care (10), it is especially important to examine both short-term (acute) and longer-term exercise effects in this population. This study was designed to evaluate the hypothesis that the physiologic arousal of acute exercise would contribute to enhanced cognitive/neuropsychologic performance among patients with COPD. It has been suggested that exercise-associated physiologic arousal may contribute to increased blood flow and neurotransmitter release, which are thought to contribute to improvements in cognitive performance (6). Thus, the study protocol required peak exercise performance in order to maximize physiologic arousal. Methodologic limitations of previous studies in this area were addressed by including a matched group of healthy older adults to control for the influence of age and education on cognitive performance. The study also utilized a laboratory setting for the exercise stimulus to ensure consistency across subjects and reproducibility of the exercise condition, and to minimize the influence of social interaction/stimulation on cognitive performance. In addition, all participants completed a video-watching condition to control for the influence of repeated testing in the exercise setting. Based on findings of previous studies, the primary hypothesis of this study was that a brief bout of exercise would be associated with greater improvements in cognitive performance than would a video-watching control condition. In particular, it was hypothesized that patients with COPD would achieve greater exercise-related changes in cognitive performance than would a healthy matched control group. In addition, prior data suggest that cognitive improvement may be most evident

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peak exercise performance after approximately 20 min. Thus, increases in workload increments were smaller than typically utilized in a standard stress test protocol. Exercise for each subject began at 0 W and was increased 5 W every 2 min thereafter, with exercise rates remaining constant at 40 to 60 rpm. Each exercise test was conducted by a Master-level Clinical Exercise Physiologist under the supervision of a cardiologist. Exercise physiologists were instructed to make minor modifications in the protocol to facilitate each subject reaching peak exercise performance as close as possible to the 20-min time frame. The concentration of expired oxygen and carbon dioxide was evaluated in breath-by-breath analysis with 30-s averages (Medical Graph ics CPX/D, St. Paul, MN) to calculate oxygen consumption (VO2) and carbon dioxide production (VCO2). Peak VO2 was calculated for each subject and expressed in milliliters per kilogram per minute. Other measurements during the exercise condition included heart rate and maximal workload performed during the exercise. Electrocardiographic rhythm strips also were monitored for arrhythmias or ischemic changes. Although the exercise lasted only 20 min, the full exercise condition required approximately 45 min including time to prepare participants for exercise and approximately 15 min for cool-down following the exercise condition. The exercise was completed in an isolated chamber with only the exercise physiologist present. Four participants utilized supplemental oxygen during the exercise condition. Oxygen saturation (SaO2) was monitored throughout the exercise activity. All but three of the participants maintained SaO2 above 90% throughout exercise. For two of the participants, SaO2 was reduced to 87% at the termination of exercise, whereas for the third participant SaO2 reached a low of 79%. Video condition. Each subject sat alone in an isolated room and watched two brief educational videotapes describing the benefits of exercise for physiologic functioning and cholesterol reduction among older adults. The first video was Heart Decisions for Life (ParkeDavis, 1990) and the second was Controlling Cholesterol Through Exercise and Fitness (Zadox, 1989). Total time required for viewing both videotapes was approximately 45 min. Assessments. Immediately prior to (pretest) and following each condition (posttest), subjects completed a brief assessment of cognitive performance. Assessments following the exercise condition were conducted after the 15-min cool-down period. The cognitive/neuropsychologic assessment was designed to evaluate aspects of cognitive functioning that have been responsive to exercise in prior studies and that measure components of executive functioning including mental efficiency, verbal processing, attention, short-term memory, and motor speed. Tests of mental efficiency included the Trail Making Test (Parts A and B), which encompasses components of perceptual motor speed and sequencing (11); the Digit Symbol subtest of the WAIS-R, a common test of psychomotor performance sensitive to brain dysfunction (12); the Verbal Fluency test of the Halstead-Reitan battery, a measure of verbal processing with excellent testretest reliability (13) sensitive to frontal lobe impairment (14); the Digit Span subtest from the WAIS-R (12), which provides a measure of attention and short-term memory; and the Finger Tapping test from the Halstead-Reitan battery, which is a reliable indicator of motor speed (15). Total score for the Trail Making Test was calculated as Part B Part A (i.e., time to complete Part B minus time to complete Part A). For the Finger Tapping test, subjects were given five 10-s trials with each hand, from which a mean score was derived for the dominant and nondominant hands. Total time required for the cognitive/neuropsychologic battery was approximately 20 min. Data analysis. Cognitive data were analyzed with repeated measures analysis of covariance (ANCOVA), with one between-subjects variable (group: COPD versus healthy) and two within-subjects variables (condition [exercise versus video] and time [pretest versus postcondition]). Covariates included physiologic variables for which there were significant group differences at baseline, as described below. The primary hypothesis of the study would be supported by a three-way interaction of group by condition by time for the Verbal Fluency test of verbal processing, with an level of 0.05.

on a test of verbal performance, and that tests of psychomotor speed and memory may not be responsive to exercise in this population (4).

METHODS
Subjects
Twenty-nine adults (17 women; 12 men) with COPD were recruited from outpatient clinics in the Columbus, Ohio, metropolitan area. Criteria for inclusion in the study were age over 55 yr, COPD diagnosis for at least 6 mo, and a ratio of FEV1/FVC 0.70. Age range of participants was 56 to 85 yr (mean age 67.8 yr [ 7.4]) and results of pulmonary function testing were consistent with a diagnosis of COPD, as shown in Table 1. In addition to the COPD group, a matched sample of healthy older adults was recruited from community senior centers. Prospective healthy control subjects were excluded from participation if they had been diagnosed with a major illness during the prior 6 mo or if they had a history of pulmonary disease, cardiac disease, or lung cancer. Healthy participants were matched with COPD participants according to age, sex, and educational status. As shown in Table 1, there were no differences between groups on the matching variables. Both study groups included more women than men, and most participants had completed at least a high school education. The overall minority representation in the study (16%) was reflective of the Columbus metropolitan area.

Procedure
The procedures utilized for this study were approved by the Biomedical Sciences Institutional Review Board. Participants completed a written informed consent agreement prior to participation in the investigation. All subjects participated in both an exercise condition and a video-viewing condition. Thus, condition (exercise versus video) served as a within-subject variable. Order of conditions (exercise or video) was randomly assigned and sessions for each condition were separated by 1 wk. Subjects proceeded through each stage of the study individually, and there was no opportunity for group social interaction. Each participant was paid $100 for completing the study, regardless of the time required. Exercise condition. Subjects completed a modified bicycle ergometry stress test with the subject sitting upright on an isokinetic, magnetically braked, bicycle ergometer (Medical Graphics Cardio2 Cycle). The exercise condition was designed to ensure that subjects would reach

TABLE 1. DEMOGRAPHIC CHARACTERISTICS, AEROBIC CAPACITY, AND PULMONARY FUNCTION*

COPD Variable Age, yr Sex Male Female Education 12 yr 12 to 16 yr 16 yr Race White African American Peak VO2, ml/kg/min FEV1 Predicted FEV1, % FVC Predicted FVC, % FEV1/FVC Mean ( SD) 67.8 (7.4) 12 (41) 17 (59) 2 (7) 16 (55) 11 (38) 27 (93) 2 (7) 13.7 (3.3) 1.18 (0.49) 43 (17) 2.34 (0.82) 67 (23) 0.51 (0.12) 16.6 (3.9) 2.48 (0.79) 94 (15) 3.19 (0.93) 96 (14) 0.78 (0.09) n (%) Healthy Mean ( SD) 68.7 (6.0) 12 (41) 17 (59) 1 (3) 20 (69) 8 (28) 22 (76) 7 (24) n (%)

Definition of abbreviations: COPD chronic obstructive pulmonary disease; peak VO2 peak oxygen consumption. * Predicted values based on norms adjusted for age, height, sex, and race. p 0.01. p 0.001.

RESULTS
As expected, there were significant between-group differences in pulmonary function (FEV1/FVC: F[1,55] 50.6, p 0.000)

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and physical endurance (peak VO2: F[1,52] 8.77, p 0.005], as shown in Table 1. To account for baseline group differences in physical endurance and pulmonary function, both variables were included as covariates in each of the cognitive analyses. Repeated-measures ANCOVA of cognitive variables indicated no effect for the Trail Making test or Digit Symbol test, but revealed a significant three-way interaction for Verbal Fluency (F[1,49] 5.96, p 0.018). Analysis of simple effects indicated improvement among subjects with COPD in the exercise condition (F[1,21] 9.88, p 0.005), with no change among subjects with COPD in the video condition or among healthy subjects in either condition. Analysis of the Digit Span and Finger Tapping results indicated no significant interaction effects. Adjusted mean scores for all cognitive tests are included in Table 2.

DISCUSSION
This is the first study to provide evidence of an acute effect of exercise on cognitive performance among patients with COPD. Results supported the hypothesis that exercise would have an acute positive effect on verbal processing, thus the data are consistent with prior research indicating significant effects of longer-term exercise on verbal processing among patients with COPD (4). The absence of exercise effects in the video control condition suggests that cognitive improvement was not reflective of practice effects. Furthermore, the absence of an effect in the healthy matched control group suggests that exercise did not have a similar acute benefit among healthy older adults. Thus, the data indicate that components of the exercise experience (e.g., increased respiration, increased blood flow, excitation of the central nervous system, neurotransmitter release) may be particularly beneficial for cognitive function among patients with COPD. Exercise was associated with improved performance only on the Verbal Fluency test, reflecting enhanced ability to sequence responses and generate words. Recent data indicate that this test is relatively free of practice effects, presumably because of low task complexity (16), further supporting its utility for this study. The absence of an effect for tests of short-term memory, attention, and psy-

chomotor speed suggests that the latter components of cognitive performance may be less responsive to exercise among patients with COPD. The exercise stimulus in this study was a laboratory-based bout of exercise in which participants were encouraged to exercise to a peak level. Hence, across participants the exercise stimulus was consistent and reproducible, and the use of such a standardized strenuous exercise protocol facilitated comparison of participants. However, there are several areas relevant for further investigation including (1) examining the influence of varying exercise intensity level and exercise duration on acute cognitive outcomes, (2) evaluating the relationship between cognitive gains associated with individual bouts of exercise and longer-term cognitive changes following multiple exercise sessions, and (3) using brain imaging techniques to evaluate changes in cerebral blood flow associated with exercise and cognitive performance. Despite enduring questions regarding the specific mechanisms by which acute exercise influences cognitive function, data from this study appear to support a biologically based model in which acute exercise is thought to enhance cognitive function via improved neurotransmitter functioning in the brain, as documented in animal models (17). These data do not support a model embracing social aspects of the exercise experience as a source of cognitive change, although social influences cannot be ruled out completely due to the presence of a technician in the exercise setting. From a practical perspective, the data suggest that a bout of strenuous exercise will have no deleterious effect on cognitive function and that patients with COPD may experience immediate positive benefits in cognitive performance associated with exercise activity. The short-term effect of relatively small increases in verbal processing ability is unknown, but increased performance on this measure reflects greater ability to organize or sequence information. This domain of cognitive functioning, in turn, is important for performance of clinically relevant behavior such as following directions for medical care.
Acknowledgment : We wish to thank Bradley Barcom and Karen Wilson, M.A., for assistance with data collection and management, and Johanna Weber, Ph.D., for assistance in preparation of this manuscript.

TABLE 2. LEAST-SQUARE MEAN ( STANDARD ERROR) COGNITIVE FUNCTIONING SCORES IN EXERCISE AND VIDEO CONDITIONS, COVARYING PEAK VO2 AND FEV1/FVC*
COPD (n 29) Exercise Pretest Trail making (B A,s) Digit symbol Verbal fluency Digits forward Digits backward Finger Tapping Dominant hand Nondominant hand 61.1 (17.5) 50.5 (3.2) 28.5 (2.4) 8.0 (0.7) 7.3 (0.7) 41.2 (1.9) 37.0 (1.4) Posttest 51.3 (11.2) 51.4 (3.1) 30.8 (2.1) 8.8 (0.6) 7.1 (0.6) 4.16 (1.8) 37.6 (1.3) Pretest 65.8 (11.5) 48.6 (3.1) 29.2 (2.2) 8.2 (0.7) 6.6 (0.6) 40.3 (2.1) 37.3 (1.5) Video Posttest 52.8 (9.9) 50.0 (3.2) 27.8 (2.2) 8.4 (0.6) 6.7 (0.7) 42.1 (1.9) 37.9 (1.4) Exercise Pretest 56.3 (14.8) 51.5 (2.8) 32.4 (2.1) 8.1 (0.6) 6.4 (0.6) 41.7 (1.7) 37.9 (1.2) Posttest 44.7 (9.4) 55.1 (2.7) 30.7 (1.9) 8.3 (0.5) 6.3 (0.5) 42.5 (1.5) 38.0 (1.2) Pretest 48.7 (9.7) 53.0 (2.7) 30.4 (1.9) 8.4 (0.6) 6.6 (0.6) 42.1 (1.8) 38.5 (1.3) Healthy (n 29) Video Posttest 44.7 (8.4) 53.2 (2.7) 32.3 (1.9) 8.3 (0.6) 6.5 (0.60) 43.7 (1.7) 39.1 (1.2)

Definition of abbreviation: COPD chronic obstructive pulmonary disease. * Higher scores indicate better performance for all tests except Trail Making. p 0.01.

Brief Communication References

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